Synthesis and Characterization of Carbon &

Nitrogen based Covalent Organic Framework

to Explore Biomedical Application

By

Bakar bin Khatab Abbasi

CIIT/FA18-R06-031/LHR

MS Thesis
In
Chemistry

COMSATS University Islamabad

Lahore – Pakistan

Spring, 2020
i
 COMSATS University Islamabad

Synthesis and Characterization of Carbon &

Nitrogen based Covalent Organic Framework
to Explore Biomedical Application

A Thesis Presented to

COMSATS University Islamabad, Lahore Campus

In partial fulfillment
of the requirement for the degree of

MS Chemistry

By

Bakar bin Khatab Abbasi

CIIT/FA18-R06-031/LHR

Spring 2020

ii
 Synthesis and Characterization of Carbon &
Nitrogen based Covalent Organic Framework
to Explore Biomedical Application
A Post Graduate Thesis submitted to the name of Department of
Chemistry as partial fulfillment of the requirement for the award of
Degree of M.S (Chemistry)

Name Registration Number

Bakar bin Khatab Abbasi CIIT/FA18-R06-

031/LHR

Supervisor Co-Supervisor

Dr. M. Shahid Nazir Dr. Sadaf-ul-Hassan

Assistant Professor Assistant Professor
Department of Chemistry Department of Chemistry
COMSATS University COMSATS University
Islamabad, Lahore Campus Islamabad, Lahore Campus
August 2020 August 2020

iii
 Final Approval
This thesis entitled

Synthesis and Characterization of Carbon &

Nitrogen based Covalent Organic Framework to
Explore Biomedical Application
By
Bakar bin Khatab Abbasi
CIIT/FA18-R06-031/LHR
Has been approved
For the COMSATS University Islamabad, Lahore Campus

External Examiner: ________________________________

Prof. Dr. Tahir Imran Qureshi
Department of Chemical Engineering Head, Environmental Sciences and Engineering
Department NFC-Institute Engineering & Technology Training, Khan-e-wal Road Multan

Supervisor: ________________________________________
Dr. M. Shahid Nazir (Assistant Professor)
Department of Chemistry CUI, Lahore Campus

Co-Supervisor: _____________________________________
Dr. Sadaf-ul-Hassan (Assistant Prof.)
Department of Chemistry CUI, Lahore Campus

HOD: ____________________________________________
Dr. Mazhar Amjad Gilani (Associate Prof.)
Department of Chemistry CUI, Lahore Campus

iv
 Declaration
I, Bakar bin Khatab Abbasi, CIIT/FA18-R06-031/LHR hereby
declare that I have produced the work presented in this thesis,
during the scheduled period of study. I also declare that I have not
taken any material from any source except referred to wherever
due that amount of plagiarism is within acceptable range. If a
violation of HEC rules on research has occurred in this thesis, I
shall be liable to punishable action under the plagiarism rules of
the HEC.

Date: 20-08-2020 Signature of the Student

Bakar bin Khatab Abbasi

CIIT/FA18-R06-031/LHR

v
 Certificate
It is certified that Bakar bin Khatab Abbasi, CIIT/FA18-R06-031
has carried out all the work related to this thesis under my
supervision at the Department of Chemistry, COMSATS University
Islamabad, Lahore Campus and the work fulfills the requirement for
award of MS degree.

Date: 20-08-2020

Supervisor:

________________
Dr. M. Shahid Nazir
Assistant Professor

Head of the Department:

______________________________
Dr. Mazhar Amjad Gilani (Associate Professor)
Department of Chemistry

vi
 DEDICATIONS
To my parents and family for their support & love.
And to my elder brother for his provision
throughout this journey.

vii
 ACKNOWLEDGEMENTS
I am highly indebted to Almighty Allah for giving me the strength and
patience to complete this work.
Firstly, I would like to express my sincere gratitude to my supervisor Dr.
Muhammad Shahid Nazir and co-supervisor Dr. Sadaf-ul-Hassan for
their suggestions and constant guidance. Their recommendations
throughout the work really helped me to timely complete this work.
I am grateful to the Head of Department of Chemistry COMSATS
University Islamabad, Lahore, Dr. Mazhar Amjad Gilani for his help
towards postgraduate affairs. I wish to express my thanks to all my friends
and colleagues especially to Ms. Sadaf Ahmad who supported and helped
me throughout my research work.

Bakar bin Khatab Abbasi

CIIT/FA18-R06-031/LHR

viii
 ABSTRACT
Synthesis and Characterization of Carbon & Nitrogen based
Covalent Organic Framework to Explore Biomedical
Application
Covalent organic frameworks (COFs) represent a class of advanced porous materials
with outstanding properties such as less density, excellent surface area, and adjustable
pore structure and size. These materials proved themselves promising in several fields
including separation science, catalysis, sensing, and biomedicine. Recently, many
techniques have been developed to synthesize different types of COFs for instance
boron-based COFs, imine-based COF, hydrazine-based COFs, and ketoenamine-based
COFs according to the nature of linkers and the purpose of application. Among these
types of COFs, imine-based COFs are found to be most potential candidate for various
applications. Major selection factors in the synthesis of COFs include stability of
monomers and facile synthesis route at room temperature. Keeping in view all the
above aspects, an imine-based COF has been synthesized at room temperature.
Triformylbenzene (TFB) and benzidine (BD) monomers reacted at reported conditions
and successfully obtained COF, donated as TFB-BD. Successful synthesis and structure
of the COF TFB-BD was confirmed by FTIR and XRD. In FTIR the C=N peak at 1617
cm-1 clearly indicated the formation of framework between the two monomers. In XRD
strongest diffraction peak at 2Ө at 2.66° presented confirmation of crystalline nature of
synthesized COF-TFB-BD. Furthermore, in SEM and TEM imaging, the
morphological characteristic showed porous nature of the prepared COF. Literature
describes the utilization of this COF may be explored for biomedical application.

Keywords
Covalent Organic Framework; COF-TFB-BD; Imine-based COF; Room temperature
synthesis; Applications; Biomedical.

ix
TABLE OF CONTENTS

1. Introduction and Literature Review ..................................................... 1

1.1. Covalent-Organic Frameworks (COFs) .................................................... 2

1.1.1. Structure of Covalent Organic Frameworks (COFs) ................................... 3

1.1.1.1. Structure of Building Blocks ................................................................ 3

1.1.1.2. Topologies for 2D Covalent Organic Frameworks (COFs) ................. 4

1.1.2. Types of Covalent Organic Frameworks (COFs) ........................................ 5

1.1.2.1. Boron based Covalent Organic Frameworks (COFs) .......................... 6

1.1.2.2. Imine-based Covalent Organic Frameworks (COFs) ........................... 6

1.1.2.3. Hydrazone and Azine-based Covalent-Organic Frameworks (COFs) . 6

1.1.2.4. Ketoenamine-based Covalent-Organic Frameworks (COFs) .............. 6

1.1.3. Synthetic Methods for Covalent-Organic Frameworks (COFs) .................. 9

1.1.3.1. Solvothermal Synthesis ........................................................................ 9

1.1.3.2. Ionothermal Synthesis ........................................................................ 10

1.1.3.3. Microwave Synthesis ......................................................................... 10

1.1.3.4. Room-temperature Synthesis ............................................................. 10

1.1.4. Applications of Covalent-Organic Frameworks (COFs) ........................... 11

1.1.4.1. Separation Science ............................................................................. 11

1.1.4.2. Gas Adsorption and Storage ............................................................... 12

1.1.4.3. Sensing ............................................................................................... 13

1.1.4.4. Catalysis ............................................................................................. 14

1.1.4.5. Biomedical Field ................................................................................ 15

1.2. Problem Statement .................................................................................. 17

1.3. Motivation ............................................................................................... 17

1.4. Objectives ................................................................................................ 17

2. Materials and Methodology.................................................................. 18

x
2.1. Synthesis of COF-TFB-BD ..................................................................... 19

2.1.1. Materials .................................................................................................... 19

2.1.2. Methodology.............................................................................................. 19

3. Characterizations .................................................................................. 21

3.1. FTIR Spectroscopy .................................................................................. 22

3.2. X-Ray Diffraction ................................................................................... 22

3.3. SEM and TEM Imaging .......................................................................... 22

3.4. DTA/TGA ............................................................................................... 22

4. Results and Discussion .......................................................................... 23

4.1. FTIR Analysis ......................................................................................... 24

4.2. XRD Analysis ......................................................................................... 25

4.3. SEM and TEM Analysis ......................................................................... 26

4.4. TGA-DTA ............................................................................................... 27

5. Conclusion and Future Outlook .......................................................... 29

6. References .............................................................................................. 31

Research Publications ..................................................................................... 43

xi
LIST OF FIGURES

Figure 1. An overview of types, synthetic methods, and applications of COFs [2]. ..... 2
Figure 2. Describes the topology of 2D COFs [8]. ........................................................ 5
Figure 3. Properties and applications of COFs [65]. ................................................... 12
Figure 4. Reported biomedical applications [96]. ........................................................ 15
Figure 5. Describes how COF was synthesized from white turbid to yellow crystals. 19
Figure 6. Centrifugation machine to obtain COF-TFB-BD solid. ............................... 20
Figure 7. Washing of COF-TFB-BD precipitates through Soxhlet apparatus. ............ 20
Figure 8. Yellow colored solid of COF-TFB-BD obtained before and after drying. .. 20
Figure 9. The FT-IR spectra of the COF-TFB-BD. ..................................................... 24
Figure 10. XRD spectrum of COF-TFB-BD ............................................................... 25
Figure 11. SEM (a,b) and TEM (c) images of COF-TFB-BD ..................................... 26
Figure 12. TGA/DTA graph of COF-TFB-BD ............................................................ 27

xii
LIST OF TABLES

Table 1. Structural features of the synthesized COFs. ................................................... 7

Table 2. Overview of Synthetic routes of COFs. ......................................................... 11
Table 3. COFs as best biomedical candidate. .............................................................. 16

xiii
LIST OF ABBREVIATIONS

COF Covalent organic framework

MOF Metal organic framework
DCC Dynamic Covalent Chemistry
BUs Building units
MC Mechanochemical
MW Microwave
LAG Liquid assisted grinding
SPME Solid phase micro extraction
SPE Solid phase Extraction
CEC Capillary Electro Chromatography
HPLC High Performance liquid Chromatography
GC Gas Chromatography
DNA Deoxyribo Nucleic Acid
TFB Triformyl Benzene
BD Benzidine

xiv
 Chapter 1
1. Introduction and Literature Review

1
1.1. Covalent-Organic Frameworks (COFs)
Over the century, interest in the field of porous substances has been developed
tremendously because of their worthy efficiency and unique utilization in gas uptake,
optoelectronics, catalysis, and energy storage. Though a range of porous substances
have been fashioned by numerous means, it has been realized hard to make organic
polymer complexes having distinct pores. However, the advent of “reticular chemistry”
marks it thinkable to build such porous substances that could be shaped by means of
topologically planned building units. The first class of these porous substances created
based on the reticular chemistry are metal organic frameworks (MOFs) that contain
metal ions or groups corresponding with organic linkers (ligands) to produce 1, 2, or 3
dimensional assemblies. The flexibility of metal ions coordination, joint with the well-
designed range of the organic ligands provides these substances huge potentials.
Furthermore, an additional class of porous substances on the ground of reticular
chemistry are covalent organic framework (COFs) that were for the first revealed in
2005, by Omer Yaghi [1]. Figure 1 shows the types, synthetic methods, and applications
of COFs.

Figure 1. An overview of types, synthetic methods, and applications of COFs [2].

2
Unlike MOFs, COFs are utmost significant and active participants of porous organic
substances that are built by means of reticular chemistry with the building units being
linked through covalent bonds [3]. COFs are made up of organic parts (units) along
with outstanding arrangement through atomic accuracy connected by covalent bonds.
Interestingly, COFs have the benefits of less density, great surface area, adjustable pore
structure and size, simply adapted functionality, and useful covalent-grouping of
building components [2].
1.1.1. Structure of Covalent Organic Frameworks (COFs)
COFs are polymers having crystalline, porous, and covalent nature, which permit to
intricate combination of organic building units into a fine assembly having atomic
precision. Nevertheless, the production of polymeric substances has commonly been
conquered by kinetically precise mechanisms that irreversibly built covalent bonds.
However, it is hard to form organic linked polymers in the form of solids consuming
irreversible processes. Contrary to this, “dynamic covalent chemistry (DCC)” enables
the reversible creation of robust covalent bonds that can be fashioned, fragmented, and
transformed. Consequently, contrasting traditional covalent bond forming, DCC is
much precise in thermodynamics and hence proposes reversible mechanism
arrangements with ‘‘error checking’’ or ‘‘proof-reading’’ features, resulting to the
development of the utmost thermodynamically firm structures. Furthermore, by means
of the DCC perception on the building of COFs, establishment of the polymer skeleton
take place together with the crystallization procedure, though the self-healing response
diminishes the occurrence of structural flaws and supports in the construction of a well-
ordered structure. Accordingly, the ultimate COF artifact owns a well-arranged
crystalline structure along with high thermodynamic strength [4].
1.1.1.1. Structure of Building Blocks
When building a COF focused on a desired topology, it is better to utilize firm and
distinct building units, which stay unchanged thru the production course [5]. To acquire
a crystal-like and well-arranged COF, building units structure should fulfil two
necessities: (1) the founding mechanism of the COF ought to be a reversible process,
(2) the building units geometry must be well conserved within the COF. Concerning
(1), the building units must hold reactive assemblies that activate dynamic covalent
bond construction, such as (a) no side reactions (irreversible) and (b) the reaction

3
scheme comprises only oligomers, monomers, and the polymers which are substitutable
in thermodynamic regulator. Concerning the second condition, the building units must
be firm by conformations, and the bond development path must be distinct [5].
In a COF frame, the symmetry and structure of framework is preprogrammed by the
connectivity and geometry of the ligands. For instance, trigonal planar ligands may co-
condense to make sheets having pores of hexagonal geometry, whereas tetragonal
connectors co-condense with straight building units make tetragonal pores. Afterwards,
these sheets construct piles to produce a one-dimensional channels framework. COFs
prepared from piled 2D sheets are normally termed two-dimensional COFs, while
three-dimensional COFs are fashioned from building units with three dimensions
connectivity, consequently constructing a 3D mesh [6]. Additionally, the stiff and
precise conformation of the building units permits the topological strategy of the COFs.
For simplicity, such building units were categorized as either one 2D or 3D centered on
basic symmetry symbolization that denotes the symmetry of directions of the reactive
clusters (explicitly, 2DC2, 2DC3, 2DC4, and 3DTd). The building unit geometry defines
the resultant COF assembly. Consequently, the arrangements for instance 3DTd + 3DTd,
3DTd + 2DC2, or 3DTd + 2DC3 may form 3D COFs with diverse crystalline space
clusters. Nevertheless, particular arrangements of 2D units (for instance, 2DC2 + 2DC3,
2DC3 + 2DC3 or 2DC2 + 2DC4) would give 2D COFs with intended topology and pore
configuration. The firm nature and distinct bonding course of arenes marks aromatic p-
schemes appropriate constructing units for COFs. The variety of aromatic schemes
permits several building unit arrangements, which gives COFs with great tractability in
their molecular theme [1].
Furthermore, the chemical and physical features of COFs majorly be determined by the
building units and the covalent linkage present between them [7].
1.1.1.2. Topologies for 2D Covalent Organic Frameworks (COFs)
Figure 2 presents the skeletons of polygon of COFs that may be developed by
congregation of firm building units as edges and vertices. The established shapes of
COF polygon comprise of hexagonal, trigonal, tetragonal, kagome, and rhombic
assemblies, and the building units may be categorized as C6-, C4-, C3-, and C2-
symmetric entities founded on the regularity of reactive clusters directionally.
Hexagonal COFs may be built by both the self-condensation of C2 symmetric blocks
and the arrangements of C3 symmetric edges and C2 or C3 symmetric blocks. Moreover,

4
the topology of hexagonal may also be constructed consuming a three-constituent two-
stage scheme which comprises two C3 symmetric loops and one C2-symmetric ligand.
Likened to the hexagonal homologues COFs of tetragonal topology founded on the
topology diagram (C4 + C2) displays prolonged π conjugation while trigonal COFs
created by means of C6-symmetric loops and C2-symmetric ligands propose great π unit
density. Furthermore, the structural contest of 4-armed vertices of C2 and linear linkers
C2 tends to two diverse assemblies: a rhombic shaped single-pore and a kagome
topology dual-pore [8].
1.1.2. Types of Covalent Organic Frameworks (COFs)

Figure 2. Describes the topology of 2D COFs [8].

5
A variety of COFs have been fashioned by the selection of the building units. By
changing the building units, different types of COFs have been obtained that are
different to each other and have different applications. Consequently, based on their
building units and structural properties, COFs are majorly classified in four major types:
boron-, imine-, hydrazine-, and ketoenamine-based COFs [2, 9]. Table 1 summaries
important types of COFs.
1.1.2.1. Boron based Covalent Organic Frameworks (COFs)
Boron-containing COFs are fashioned by one self-condensation protocols of boron
acids or the other condensation per catechols, establishing boronate esters [10]. Boronic
acids self-condensation to boroxine rings and boron acids, catechols co-condensation
to boronic esters were the first protocols stated for the production of COFs. Examples
of boron-based COFs include COF-1, COF-5, TDCOF-5, TPE-Ph COF, COF-202, and
CTC-COF [6].
1.1.2.2. Imine-based Covalent Organic Frameworks (COFs)
The condensation of amines and aldehydes produces imine bonds. Such bonds possess
noteworthy greater stability as compared to the boron esters, therefore assembling
subsequent imine-based COFs for a wider series of applications. Besides, after an
aromatic amine reaction with an aromatic aldehyde, the attained product is a
conjugation of the π systems of two linkers, allowing conjugation above entire 2D COF
sheets. Examples of imine-based COFs include COF-LZU1, IISERP-COF2, NUS-14,
COF-SDU1, SIOC-COF-8, 3PA-TT COF, and COF-DHTA [6].
1.1.2.3. Hydrazone and Azine-based Covalent-Organic Frameworks (COFs)
Hydrazides co-condense reversibly with aldehydes to produce hydrazones, therefore
allowing the usage of this association for COF production. Hydrazone COFs signify a
small class of structures which have been mostly employed in catalysis and sensing.
Examples of hydrazine-based COFs include COF-42, COF-43, TFPT-COF, LZU-21,
and NUS-3 [6].
Whenever hydrazine is utilized as N-containing coupling companion for aldehydes, an
azine link is formed. Examples of azine-based COFs include Py-Azine COF, HPCOF-
1, HPCOF-2, COF-JLU3, HEX-COF 1, and LZU-22 [6].
1.1.2.4. Ketoenamine-based Covalent-Organic Frameworks (COFs)
Aldehyde connector for the COF production has been testified. This building unit
features hydroxyl (OH) assemblies contiguous to the formyl clusters. During the COF

6
 synthesis, initially an imine COF is made that may then experience an irretrievable
tautomerization (enol-keto) to establish a ketoenamine association, therefore
designated ketoenamine COFs. Examples of ketoenamine-based COFs include DABH-
TFP COF, NUS-10, Azo-COF, and BF-COF-2 [6].

Table 1. Structural features of the synthesized COFs.

Type COF Pore size (nm) SBET (m2 g-1) Reference

Boron-based COF-202 1.1 2690 [11]
CuP-COF 2.5 1894 [12]
ZnP-COF 2.5 1724 [12]
H2P-COF 2.5 1713 [12]
CTC-COF 2.3 1894 [13]
ZnPc-PPE COF 4.4 1710 [14]
ZnPc-NDI COF 4.0 440 [14]
ZnPc-DPB COF 3.4 490 [14]
ZnPc-Py COF 2.7 485 [14]
COF-66 2.3 420 [15]
BTP-COF 4.0 2000 [16]
NiPc COF 2.3 776 [17]
TP-COF 3.2 868 [18]
COF-18Å 1.8 1263 [19]
COF-16Å 1.6 753 [19]
COF-14Å 1.4 805 [19]
COF-11Å 1.1 105 [19]
COF-10 3.2 1760 [20]
COF-8 1.6 1350 [20]
COF-6 0.9 750 [20]
COF-108 1.9,3.1 --- [21]
COF-105 2.1 --- [21]

7
 COF-5 2.7 1590 [22]
COF-102-allyl --- --- [23]
COF-102-C12 --- >2000 [23]
PPy-COF 1.7 923 [24]
COF-103 1.2 4210 [21]
COF-102 1.2 3472 [21]
COF-1 0.7 711 [22]
Imine-based HPB-COF 1.2 965 [25]
Py-An COF 2.4 1497 [26]
Py-2,2ʹ-BPyPh 2.8 2349 [27]
Py-DHPh1.6 2.4 1895 [27]
COF
CuP-TFPh50 2.5 1389 [28]
COF
DhaTph COF 2.0 1305 [29]
EB-COF:Br 1.7 774 [30]
COF-LZU8 1.3 454 [31]
TpPa-Py 1.5 370 [32]
TPB-DMTP- 3.3 2105 [33]
COF
TpBDH COF 2.4 642 [34]
CTV-COF-1 1.6 1245 [35]
Tp-Azo COF 2.7 1328 [36]
TpPa-1 1.8 535 [37]
COF-43 3.5 620 [38]
COF-42 2.8 710 [38]
COF-366 2.0 735 [15]
COF-LZU1 1.8 410 [39]
COF-300 0.8 1360 [40]

8
Imide-based PI-COF-2 5.3 2346 [41]
PI-COF-3 3.7 1297 [41]
Triazine-based CTF-1 1.3 791 [42]
CTF-2 2.0 90 [43]
Azine-based ACOF-1 1.1 1176 [44]
COF-JLU2 1.1 410 [45]
Py-Azine COF 1.9 1210 [46]
Phenazine-based CS-COF 1.6 776 [47]
Hydrazone- TFPT-COF 3.8 1185 [48]
based

1.1.3. Synthetic Methods for Covalent-Organic Frameworks (COFs)

For the synthesis of COFs, not only selection of building units is important but also the
synthetic route is very essential. Ever since Yaghi along with his colleagues subjugated
the solvothermal technique to accomplish the leading achievement in the COF
production, several scholars have tried to enlarge the production probability in diverse
means [2]. Nothing matters which kind of building units, a facile strategy can make it
possible for industrial production. In the beginning COFs were synthesized by
solvothermal process but now a days, various methods like ionothermal [49],
microwave heating [50], room-temperature synthesis [51], and sonochemical synthesis
[52] are used to synthesize COFs (Table 2) [53].
1.1.3.1. Solvothermal Synthesis
The solvothermal designing of COFs depends on thermal or heat energy to encourage
the reaction equilibrium route for thermodynamically firm crystalline yields [54]. The
solvothermal production technique is utmost frequently utilized method to manufacture
COFs. Alike production of inorganic zeolites in autoclaves, the production of COF
precipitates by means of the solvothermal technique generally takes two to nine days
and entails heating in an sealed vessel (80 to 120 ℃) [55]. However, solvothermal
production involves prolonged process time and great energy feed. To overcome such
difficulties, alternate energy sources for instance microwave, mechanical agitation,
ultrasound, electron beam, and light irradiation have been used to speed up the
crystallites nucleation and therefore improve the complete synthetic level of COFs [54].

9
1.1.3.2. Ionothermal Synthesis
In 2008, Thomas and coworkers created porous crystalline COF through the
ionothermal technique for the first time. However, due to the condition of greater
reaction temperature that bounds the variability of assembly blocks, the progress of
ionothermal production is still very restricted so far [55].
1.1.3.3. Microwave Synthesis
Microwave assisted production has stimulated huge attention because of its exclusive
characteristics for instance faster reaction rates, lesser energy intake, and greater profits.
In year 2009, a scientist named Cooper along with his group testified for the foremost
time, the microwave assisted production of boron ester-based COFs in microwave
irradiation at 100 ℃. COFs for instance COF-5, COF-102, BTD-COF, TpPa-COF-
MW, and THCOF have been successfully synthesized via microwave method [54].
Even though the progress in the microwave supported production of COFs are relatively
restricted, it has been recognized in multiple circumstances that the microwave assisted
production not only deals an prompt alternate development to the traditional procedures
but also gives the acquired COFs with splendid performance [54].
1.1.3.4. Room-temperature Synthesis
Reaction temperature is one of the supremely significant tentative circumstances in the
production of COFs. Coincidentally, latest research attainments have established a
revolution and many novel synthetic approaches for COFs have been described that can
be comprehended at room temperature. Basically, room temperature production
comprises mechanochemical (MC) formation and rapid solution-phase formation.
Mechanochemical (MC) formation has an improving rank as a substitute synthetic
method since its reaction route is fast and eco-friendly. Through Schiff base MC
grinding by means of a mortar and pestle, chemically steady imine-linked COFs have
been manufactured. Furthermore, liquid-assisted grinding (LAG) technique has been
active for making of hydrazone-based COF. Furthermore, a modest and superficial
room-temperature solution-phase way for the assembly of COFs for instance TpBD and
Sc(OTf)3, has been reported [56].

10
 Table 2. Overview of Synthetic routes of COFs.

Method COFs Conditions for Synthesis SBET (m2 g-1) Reference

Room- MF-COF-1 Standard room temperature 535 [57]

Temperature and atmospheric pressure
(ambient) RT-COF-1 Room temperature 329 [58]
Synthesis COF (TpPa-1 Grinding at RT for 45 min 35-61 [59]
and TpPa-2)
COF25 Room temperature storage 1523 [60]
for two days
Solvothermal COF-1 Temp: 120oC for 72 hours 711 [22]
Synthesis COF-5 Temp: 120oC for 72 hours 1590 [22]
COF-18 Temp: 120oC for 72 hours 1260 [61]
COF-102 Temp: 85oC for 4 days 3472 [21]
Microwave COF-102 Temp: 100oC for 20 min 2926 [62]
Synthesis COF-5 Temp: 100oC for 20 min 2019 [62]
Ionothermal CTF-1 Temp: 400oC for 10 hours 791 [42]
Synthesis IL-COFs Ambient temperature for 517-870 [63]
12 hours

1.1.4. Applications of Covalent-Organic Frameworks (COFs)

Owing to excellent surface area, huge porosity and crystal-like structure, COFs have
appeared as favorable candidate to be used in many fields [7], as shown in Figure 3.
Some of the emerging applications of COFs are elaborated below.
1.1.4.1. Separation Science
COFs have been utilized as auspicious sorbents for pre-treatment of sample for instance
solid-phase extraction (SPE) and solid-phase microextraction (SPME), and as
innovative inert phases for chromatography counting high-performance liquid
chromatography (HPLC), capillary electrochromatography (CEC), and gas
chromatography (GC) [64].

11
 Figure 3. Properties and applications of COFs [65].

The COFs utilized in science of separation display numerous properties. Presently, two-
dimensional COFs are utilized in separation science, within which the building units
bond to yield prolonged linkages having hexagonal geometries. Certain COFs, for
instance COF CTF-1, COF TpPa-2, COF CTpBD and COF-1, can openly be used as
remarkable sorbents for SPE. Yet, many of the COFs are required to be modified to
mark them additionally adequate for diverse analytical implements. The strong covalent
linkages and the multifaceted COFs guarantee the enormous adsorption capability and
decent lifetime of the COF-centered SPME substances. Chiral COFs have been utilized
in GC. Nonetheless, COFs manufactured through outdated approaches frequently
display uneven form, size in sub micrometers, or comprehensive size distribution, that
is the extreme ultimatum for the use of COFs in HPLC. Open-tube CEC (OT-CEC),
amongst most corporate CEC modes, has small column capability and an insufficient
phase ratio. But, the characteristic of near alteration with porous compounds of OT-
CEC column offers COFs great viability to overcome the deficiencies owing to the
great surface area and plentiful organo-functional clusters of COFs [64].
1.1.4.2. Gas Adsorption and Storage
Scholars have courage to substitute fossil fuels for an energy foundation by means of
porous components as basins for storage and uptake of hydrogen, methane, and carbon
dioxide (CO2). Thus, environmental complications initiated by extreme CO2 releases
could be solved. Interestingly, COFs could compress gas molecules within pores of
their structure. Additionally, likened to other porous substances (Maxsorb and

12
Zeolites), COF components have the benefit of less density, great enduring surface
areas, extraordinary thermal and chemical strength, columnar π-stacking assembly,
adjustable pore structure and size and adaptable covalent arrangement of building
blocks. Furthermore, various outstanding works have upheld that COFs own greater
capability for the storing and separation of main gases for instance CO2, methane, and
hydrogen. In an assembly of a COF, three-dimensional COFs with greater surface area
with pore capacities showed more storing capabilities likened to two-dimensional
layered configurations [66].
Many fortitudes have been focused in current times on improvement of CO2 uptake
efficiency of COFs, and growing research has generated positive consequences.
Certainly, superior surface areas, sophisticated pore sizes and improved fundamental
reliability with small CO2 capture at lower pressure have been witnessed in
boron/imine-based and boron-based COFs, however great CO2 adsorption capabilities
and great CO2/N2 discernment have been found in triazine-based and imine-based
COFs, by apposite adsorption heat preferring the renewal of these substances. In
expressions to chemical and aqueous stability, it could be partly concluded that together
triazine-based and imine-based COFs would obligate wider projections for
implementation in CO2 uptake. COFs for instance COF-102, COF-108, PCTF-5, FCTF-
1, CTF-FUM, MCTP-1, TpBD COF, ACOF-1, COF-JLU2, COF-TpAzo, NTU-COF-
2, and ILCOF-1, have been employed successfully in the field of CO2 capture [67].
Recently, numerous groups explored that certain COFs stock larger quantities of H2
comparative to MOFs through the simulation of H2 acceptance conduct of COFs. COFs
utilized for storage of H2 include COF-1, COF-105, COF-6, COF-102 etc. Furthermore,
COFs such as COF-6, COF-102, COF-8, and COF-3 have been found promising
candidate for storage for methane gas [66].
1.1.4.3. Sensing
It has been reported that COFs show excellent luminescence properties [68-71]. Most
importantly, COFs possess low densities and high thermal and chemical stabilities.
Fluorescent COFs show high π-conjugated building block elements like triazine,
pyrene, phenyl, triphenylene, and tetraphenylene. In addition, π conjugated
arrangement might be improved by the construction of -C=N-N=C- and -C=N- bonds
[72]. First reported fluorescent COF was TP-COF [18]. Fluorescent COFs have many
applications in the field of sensing. For example, imine-linked COFs have more

13
application in the field of biosensing [73] because they may absorb DNA and protein
due to their high interactions. COFs have been found attractive and promising materials
in sensing application due to their electron rich linkers and absorbability [74].
The release of toxic and heavy metals ions like Pb2+, Cu2+, Fe3+, and Hg2+ into
environment causes diseases [75-77]. Thus, it is necessary to detect these toxic and
heavy metal ions. COFs has significant use in the recognition of metal ions [78-81].
In the field of analytical chemistry, explosives have attained great concern due to their
harmful effects on society and health of humans [76, 82-85]. For this reason, detection
of explosives is very essential. Fluorescence based COF had been studied by
researchers for the detection of the explosives [34, 86-88]. The first reported fluorescent
COF for the detection of explosives was SNW-1 [89].
Later on, many COFs have been synthesized and successfully employed in the
application of sensing such as Py-TPE COF, TPE-Ph COF, SNW-1, Py-Azine COF,
TpBDH-COFs and TfpBDH-COFs, PI-COF, COF-JLU3, COF-LZU8, and Fe-por-
COF [55].
1.1.4.4. Catalysis
The porous materials have been exclusively used for heterogeneous catalysis because
they have large surface area. For example, inorganic zeolites had been applied as
catalysis in the refining industries [90]. Amorphous inorganic polymers have become a
new candidate for catalysis [91, 92]. Recent research presented some porous materials
such as MOFs used in catalysis [93, 94]. Meanwhile, porous COF-based materials have
potential application in the field of catalysis [39]. In the interim, utilizing COFs as
heterogeneous catalysts could have the accompanying favorable circumstances,
including (i) improved catalytic reactivity because of the spatial partition of various
synergist positions in the structure, supplying COFs with helpful catalysis character;
(ii) porous channels, permitting the simple access of substrates to the chemically
dynamic locales inside the COF pores, providing the compound reactions with the size,
shape, enantio, or chemo selectivity; (iii) because of the adaptability and components
of system in solid state, by an either physical, synthetic, or a natural strategy, could get
advanced COF applications. COFs such as COF-LZU1, Cu‐COFHX and Cu‐
COFDMF, [HC≡C]x‐H2P‐COFs, chiral Zn(salen)‐based COFs, Py‐COFs, COF‐TpBpy,
CCOF‐MPC, and CTFs have been successfully utilized in catalysis [95].

14
1.1.4.5. Biomedical Field
The privileges of COFs in drug delivery, photothermal therapy (PTT), biosensing,
photodynamic therapy (PDT), bioimaging (BI) and several others (Figure 4) have been
well reported in literature [96]. Table 3 presents COFs reported in biomedical
applications.

Figure 4. Reported biomedical applications [96].

As a substitute of old-fashioned covalent bonds, physical interactions, and coordinate
bonds, COFs use active covalent bonds as associations that can save their assembly in
ordinary circumstances and be fragmented by prompts of acid. Such features mark
COFs sufficiently to reserve their assembly beforehand realization of targeted tissues
and biodegrade afterwards completing their job [96].
Interestingly, three dimensional COFs (PI-COF-4 and PI-COF-5) with controlled pore
size have been constructed [97]. In comparison of both 3D-COFs, PI-COF-5 had
reduced pore size than that of PI-COF-4 and showed lower drug release. These COFs
were studied under the control release of ibuprofen drug. Later, Zhao et al. reported
two novel COFs (PI-2-COF and PI-3-COF) [98] for control release of different drugs
for instance ibuprofen, 5-fluorouracil, and captopril. Meanwhile, a stable COF (TTI-

15
COF) for controlled drug release has also been reported [99]. TTI-COF is an imine
linked and non-toxic COF for human cells. TTI-COF has been studied for control
release of quercetin drug [100]. Imine-linked COF (COF-LZU1) showed better stability
and biocompatibility for biomedical application. In addition, a photosensitive COF had
been made that exhibited tumor growth [101].

Table 3. COFs as best biomedical candidate.

Applications COFs Reference

Drug Delivery PI-2-COF; PI-3-COF [98]

DOX@COF [102]
COF-1 [103]
TTI-COF [99]
TpASH-COF [104]
5-FU@TpASH-FA [105]
Photodynamic COF-808 [101]
Therapy COF-909 [101]
TAPT-DHTA-COF [106]
UCNP@COF [107]
Photothermal Py-BPy-COF [108]
Therapy COF-CuSe [109]
COF-909 [110]
COF-Ag2Se [111]
LZU-1-BODIPY-2I [100]
Mix Mode VONc@COF-Por [112]
Application COF-366 [113]
ICG@COF-1@PDA [114]
TP-Por [115]
TP-Por [116]

The prepared COF was constructed by inactive molecular building blocks.

Photothermal therapy is an important cancer therapy that uses photothermal agents. In

16
photothermal therapy material absorb light, causes increase in temperature that kills
tumor cells [117]. TpBD COF with combination of polythermal agents had been
utilized in phototherapy [118]. Fe3O4@TpBD COF was successfully prepared for the
photothermal therapy of cancer cells. In addition, various COFs like COF-Ag2Se [111],
and COF-CuSe [119] for biomedical applications has been reported.
From the literature review it is concluded that imine type COF could be synthesized
for selected biomedical application. Furthermore, its synthesis also brought possible
at room temperature.

1.2. Problem Statement

From literature review this is concluded as: Metal organic frameworks (MOFs), were
numerously reported in the biomedical field but have the limitation of toxicity due to
leaching effect of heavy metals and linkers.

1.3. Motivation
To solve the problem of heavy metal toxicity and its leaching may be reduce by using
newly developed COFs.

1.4. Objectives
1) To synthesize and characterize carbon- and nitrogen-based COF.
2) To explore the biomedical applications of prepared COF.

17
 Chapter 2

2. Materials and Methodology

18
2.1. Synthesis of COF-TFB-BD
2.1.1. Materials
All chemicals purchased Benzidine (C12H12N2, >96%) Sigma Aldrich; 1,3,5-
Triformylbenzene (TFB, >98.5%) Sigma Aldrich; 1,4-dioxane (C4H8O2) Sigma
Aldrich; acetic acid (CH3COOH) Sigma Aldrich; Tetrahydrofuran (THF) Sigma
Aldrich; and Ethyl alcohol (C2H5OH) Sigma Aldrich), were of analytical mark and
used without and further purification
2.1.2. Methodology
To synthesize COF-TFB-BD; a simple procedure [120] reported in literature was
followed. Firstly, 16 mg (0.15 mmol) of 1,3,5-triformylbenzene (TFB) was taken in a
glass vial. Furthermore, 1 ml of 1,4-dioxane was poured into the glass vial to get TPB
dissolved via ultrasonic agitation for 10 minutes. Afterwards, 27 mg (0.10 mmol) of
benzidine (C12H12N2) was further added into the same vial containing TFB solution
and then the mixture was agitated ultrasonically for additional 10 minutes. Moreover,
0.2 ml of beforehand prepared 3M acetic acid (aqueous) was added drop by drop into
the mixture and was placed uninterrupted at room temperature, carefully for three
days.

Day-1 Day-2 Day-3

Figure 5. Describes how COF was synthesized from white turbid to yellow crystals.

After three days, the acquired solid product was soaked in 5 ml of tetrahydrofuran
(THF) for 24 hours and was then collected through centrifuging. Afterwards, the solid
obtained was thoroughly washed with THF (5 ml) and with ethyl alcohol (5 ml), three
to four times each. At the end, the obtained solid was dried under vacuum in an oven
at 80 ℃ for 12 hours. The obtained yellow colored powder was ultimately COF-TFB-
BD.

19
 Figure 6. Centrifugation machine to obtain COF-TFB-BD solid.

Figure 7. Washing of COF-TFB-BD precipitates through Soxhlet apparatus.

Before drying After drying

Figure 8. Yellow colored solid of COF-TFB-BD obtained before and after drying.

20
 Chapter 3

3. Characterizations

21
Characterization analyses of COF-TFB-BD were accomplished by FTIR, XRD, SEM,
TEM, and TGA/DTA techniques.

3.1. FTIR Spectroscopy

FTIR is an efficient, non-destructive, simple and affordable method. IR range is
relevant to the organization of compound and its functional features. FTIR of COF-
TFB-BD was recorded by the “Thermofisher Nicolet iS50infrared spectrometer”. The
sample was in dried form and compressed by KBr powder. The scanning ranges from
4000 to 500 per cm.

3.2. X-Ray Diffraction

Powder X-Ray Diffraction (PXRD) is a simple and significant type of technique, a non-
destructive method to check about the inner structure of materials either it’s crystalline
or amorphous. It is not only limited to give data on structure but also provide texture
orientation, angle directions or crystal defects. Data of the COF-TFB-BD were
collected and characterized by the “PANalytical X-Pert Pro-diffractometer” functioned
at 40kv and 40mA with Cu kα radiation (size of step: 0.017°, time of step: 10.34 s).and
analyzed step between 5 and 80° (2ϴ), step 0.04° and 2 sec per step.

3.3. SEM and TEM Imaging

Scanning electron microscope (SEM) is significant technique to know about
morphology of the material. Observations for SEM were done and collected by Hitachi
S-4800 microscope operated at the rate of 5.0kV. Images were scanned at magnification
of 10 µm and 5 µm. Observations for TEM were done and collected by JEM-2100F
field emission transmission electron at 200 kV of accelerating voltage. Images were
scanned at magnification of 100 µm.

3.4. DTA/TGA
Thermogravimetric analysis is a technique to know about the thermal stability of the
material which is measured by mass loss in concern to temperature and time. Samples
were analyzed on a TGA Instrument Q-500 series thermal gravimetric analyzer (TGA)
with samples holding in a platinum pan under flow rate of 10mL per min in nitrogen
atmosphere using a 5 ℃ min-1 ramp rate.

22
 Chapter 4

4. Results and Discussion

23
4.1. FTIR Analysis

Figure 9. The FT-IR spectra of the COF-TFB-BD.

Figure 9, FTIR spectrum of COF-TFB-BD revealed characteristics peaks. The intense

peak of C=N appeared at 1617 cm−1 gives basic information of the final product
synthesis that is the covalent bonding was developed between the two monomers and
COF was formed. The C=N is the decisive bond for the combination of monomers and
confirmation of the final COF. The peaks around 1690 cm−1 is because of C=O bonds.
In spectra, the characteristic N-H stretching peaks of the free (unreacted) diamine
(3196-3376 cm−1) wiped out thus showing depletion of the diamine and a new peak
built at 1584 cm−1 was allocated to the C=C stretching. The C-N peak stretch is visible
at 1253 cm−1. FTIR spectra, suggests that COF-TFB-BD has been successfully
synthesized and the room-temperature facile method approach is quicker method to
develop the covalent bonds between the reacting monomers hence may increase the
degree of polymerization.

24
4.2. XRD Analysis

Figure 10. XRD spectrum of COF-TFB-BD

Powder X-Ray diffraction (PXRD) results approved the construction of a crystalline

material. The PXRD exhibited the strong peak at 2θ at 2.66° that confirmed the
crystalline nature of our prepared COF-TFB-BD. This material was synthesized via
simple method at ambient conditions exhibited starting peak as highly intense which
may be due to 2D layers stacking ordered. Peaks at 2θ of 2.66° correspond to the (100)
plane reflection and the wide peaks with 2θ of 25.45° refer to the (001) plane. The sharp
and strong XRD peak exhibited at 2.66° can be allocated to 100 facets. As compared to
the 0.6 ml 3M HOAc the 0.4 ml 3M HOAc and 0.1 ml 3M HOAc shows relatively more
intense peaks this might be due to more stacking pattern between the COF layers. As a
result, the reflection related to the plane 100 became stronger. The peak near 25° is by
reason of reflection by the (001) plane.
If we talk about the comparison of the three patterns of XRD due to difference in
concentrations of acetic acid (HOAc), we have to say this, without assistance of an acid
catalyst no condensation material can be observed. So, presence of acid catalyst like
acetic acid (HOAc) is necessary but variation in the concentration of the aqueous 6.0
M acetic acid affects the crystallinity, because more acid concentration reduces the

25
crystallinity of the material and thus exhibiting less intense peak. Even combining the
1, 4-dioxane and mesitylene in other ratios will lead to low crystallinity and the peak
intensity will become lower. Therefore, the most important step to make crystalline
COF is the ratio of acid concentration with the solvent combination for ambient room
temperature synthesis. In our COF-TFB-BD, the 0.1 ml of 3M HOAc is the suitable
combination with solvents (1,4-dioxane and mesitylene) to get maximum crystallinity
that is intense peak as seen in the PXRD pattern.

4.3. SEM and TEM Analysis

Figure 11. SEM (a,b) and TEM (c) images of COF-TFB-BD

Scanning electron microscopy (SEM) and Transmission Electron Microscopy (TEM)

images of COF-TFB-BD showed a significant layered-morphology of the material, the
morphological patterns revealed that this COF TFB-BD material has large surface area
and porous nature. While, to know about depth of porous textures scanning through
TEM was required, that gave information more deeply. In these porous materials
(COFs), the pores and their surface area really matters a lot specifically if we are

26
planning towards biomedical (Drug load/release, nanomedicines, antitherapeutic,
biosensing). No one can actually claim about the surface area, texture and porous
modification of any COF as the final because in these materials even minor
modifications in the synthesis method lead to modify these morphological properties.
In our COF-TFB-BD, the surface area is looking dispersed and also looking porous
nearly similar to other nanostructures but layered morphology of our synthesized COF
TFB-BD is really significant from many porous materials. One important reason of this
claim is that, the Nitrogen based 2D COFs really have high monodispersity then their
cousin types. This is the reason, due to which they are efficient in many applications.
The significant crystallinity of our COF TFB-BD is visible here in SEM and TEM, and
it is also evident by the intense and sharp PXRD peak. More the crystalline nature of
COF more will be surface area due to high polymerization degree which has been
already showed from the FT-IR spectra.

4.4. TGA-DTA

Figure 12. TGA/DTA graph of COF-TFB-BD

Being curious about the potential of thermal activation of synthesized COF TFB-BD,
after synthesis of this material we dried it for 12 h at 80 °C in a vacuum oven and no
significant mass loss during that heating is seen but it is noticed that thorough heating
is necessary for the removal of moisture and residual solvents from such framework
material even under vacuum.

27
When testing about the thermal stability was done we observed that the COF TFB-BD
was quite stable below 280 °C and significant mass loss was detected near 280 °C.
Above this temperature COF TFB-BD was no more stable. Along with thermo
gravimetric analysis (TGA), Differential temperature analysis (DTA) plot was also
observed. DTA graph is represented as dotted-line plot in Figure 12. DTA curve also
showed a significant range covering some region to register the changes in material
where no loss of mass occur say change in crystallinity of the COF and melting of COF,
that region starts from the 250 ℃, which indicates that after 250 ℃ of temperature the
structure of COF TFB-BD was no more stable even without mass loss before 280 ℃.

28
 Chapter 5

5. Conclusion and Future Outlook

29
Conclusion
Prepared COF TFB-BD comprised of two monomers that were triformylbenzene and
benzidine. Successful synthesis of the COF TFB-BD was confirmed by different
characterization techniques.
In FTIR, the C=N peak at 1617cm-1 evidently indicated the formation of framework
TFB-BD and the imine bonds in COF are developed completely.
In XRD strongest diffraction peak at 2θ at 2.66° showed the crystalline nature of our
material. It is the also evident that starting peak is such an intense peak due to 2D
layered stacking in our material.
In SEM and TEM imaging the layered-morphological aspect is clearly showing
crystalline and porous nature of the prepared COF.

Future Outlook
Future perspective is about to explore the biomedical application of the prepared COF.
Major target is to explore the stability, biocompatibility, and drug delivery of the
synthesized COF. As one of my junior is proceeding this work with me ahead.
Hopefully, this will show great results which would be a new platform for researchers
in this area.

30
 Chapter 6

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 Research Publications

Review Articles

i. Bakar bin Khatab Abbasi, Sadaf Ahmad et al., Bio-Nanocomposites for Heavy
Metals Adsorption and Removal in Wastewater Treatment. (In progress)
ii. Awais Ali Aslam, Bakar bin Khatab Abbasi, Sadaf Ahmad et al., A Review on
Covalent Organic Frameworks: Synthesis and Applications. (In progress)
iii. Sadaf Ahmad, Bakar bin Khatab Abbasi et al., Polysaccharides envisioning
Future Applications. (In progress)

Book Chapters

i. Sadaf Ahmad, Bushra Anees Palvasha, Bakar bin Khatab Abbasi et al.,
Polysaccharides: An Efficient Tool for Fabrication of Inorganic Materials, in:
“Polysaccharides: Properties and Applications”, Wiley-Scrivener, 2020. (Under
minor revision)

ii. Sadaf Ahmad, Bakar bin Khatab Abbasi et al., Desalination by Membrane
Distillation, in: Sustainable Material Systems for Membrane Desalination,
Springer, 2020. (Under minor revision)
iii. Bushra Anees Palvasha, Bakar bin Khatab Abbasi et al., Bioconversion of Straw
Biomass into Bio-products, in: “Bioconversion of Waste to Value Added
Products”, Springer, 2020. (Under minor revision)

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